Asymmetric synthesis is becoming of greater and greater importance, particularly in the pharmaceutical industry. Increasingly, regulatory agencies are looking to have racemic active agents resolved into their respective enantiomers and only have the active enantiomer approved for marketing. Clearly, the mere ability to resolve a racemic mixture is important, but without a means to convert the non-active enantiomer to the active one, or a chiral synthesis, clearly 50% of the yield is lost at this point alone. Even where a resolution technique is available, it may frequently result in substantial losses in yield, or introduce an undesirable solvent into the manufacturing process. Hence, there is a continuing need for chiral synthetic pathways which yield the desired enantiomer in suitably high yields and purity thereby avoiding the significant losses of product and avoiding undesirable solvents that are otherwise associated with non-asymmetric synthetic techniques.
Recently, the asymetric synthesis of benzhydrols has attracted considerable interest. Recent literature in this field has disclosed (1) asymmetric reduction of benzophenones with chiral Grignard reagents (Guette, et al., Tetrahedron 1979, 35, 1807-1815) or with lithium-aluminum hydride-chiral amino alcohol complexes (Brown et al, Tetrahedron: Asymmetry 1992, 3, 841-844 and Brown et al, Tetrahedron:Asymmetry 1991, 2, 339-342); (2) addition of chiral titanium reagents to aromatic aldehydes (Wang et al., Synthesis 1989, 291-292); and (3) resolution of benzhydrols by complexation with brucine (Toda et al., Tetrahedron: Asymmetry 1991, 2, 873-874).